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2000 | 47 | 3 | 751-762
Article title

Transport of glutathione-conjugates in human erythrocytes.

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Abstracts
EN
The last step of detoxification of both endogenous and environmental toxicants is typically a conjugation that produces a bulky hydrophilic molecule. The excretion of such conjugates out of cells is of sufficient biological importance to have led to the evolution of ATP-driven export pumps for this purpose. The substrate specificity of such transporters is broad, and in some cases it has been shown to include not only anionic conjugates but also neutral or weakly cationic drugs. In the present article, we review the molecular identity, functional and structural characteristics of these pumps, mainly on the example of human erythrocytes, and discuss their physiological role in detoxification and in the multidrug resistance phenotype of cancer cells.
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Year
Volume
47
Issue
3
Pages
751-762
Physical description
Dates
published
2000
received
2000-08-22
Contributors
  • University of Texas Medical Branch at Galveston, Department of Human Biological Chemistry and Genetics, 7.138 Medical Research Building, Route 1067, Galveston, Texas 77555-1067, U.S.A.
  • University of Texas in Arlington, Arlington, Texas, U.S.A.
author
  • Departments of Internal Medicine and of Biochemistry & Molecular Biology, University of Arkansas for Medical Sciences, and VA John McClellan Memorial Hospital, Little Rock, Arkansas, U.S.A.
  • University of Texas Medical Branch at Galveston, Department of Human Biological Chemistry and Genetics, 7.138 Medical Research Building, Route 1067, Galveston, Texas 77555-1067, U.S.A.
References
  • 1. Williams, R.T. (1959) Detoxification mechanisms; in The Metabolism and Detoxification of Drugs, Toxic Substances and Other Organic Compounds. John Wiley & Sons, NY.
  • 2. Jakoby, W.B. (1978) The glutathione S-transferases: A group of multifunctional detoxification proteins. Adv. Enzymol. Mol. Biol. 46, 383-414.
  • 3. Chasseud, L.F. (1979) The role of glutathione and glutathione S-transferases in the metabolism of chemical carcinogens and other electrophilic agents. Adv. Cancer Res. 29, 175-274.
  • 4. Mannervik, B. & Danielson, U.H. (1988) Glutathione S-transferases structure and catalytic activty. CRC Crit. Rev. Biochem. 23, 283-337.
  • 5. Hayes, J.D. & Pulford, D.J. (1995) The glutathione S-transferase supergene family: Regulation of GST and contribution of isozymes on cancer chemoprevention and drug resistance. Crit. Rev. Biochem. Mol. Biol. 30, 445-600.
  • 6. Awasthi, Y.C., Sharma, R. & Singhal, S.S. (1994) Human glutathione S-transferases. Int. J. Biochem. 26, 295-308.
  • 7. Monks, T.J., Lau, S.S., Highet, R.J. & Gillet, J.R. (1985) Glutathione conjugates of 2-bromohydroquinone are nephrotoxic. Drug Metab. Dispos. 13, 553-559.
  • 8. Ebron-McCoy, M.T., Nichols, H.P., Andrews, J.E. & Kavlock, R.J. (1995) Profile of procarbazine-induced embryotoxicity in an embryo hepatocyte co-culture system and after in utero glutathione depletion. Teratog. Carcinog. Mutagen. 15, 33-42.
  • 9. Awasthi, S., Srivastava, S.K., Ahmad, F., Ahmad, H. & Ansari, G.A. (1993) Interaction of glutathione S-transferase with ethacrynic acid and its glutathione conjugate. Biochim. Biophys. Acta 1164, 173-178.
  • 10. Bilzer, M., Krauth-Siegel, R.L., Schirmer, R.H., Akerboom, T.P., Sies, H. & Schulz, G.E. (1984) Protein, structure interaction of a glutathione S-conjugate with glutathione reductase. Kinetic and X-ray crystallographic studies. Eur. J. Biochem. 138, 373-378.
  • 11. Awasthi, Y.C., Awasthi, S. & Zimniak, P. (1997) Multiple transport proteins involved in the detoxification of endo and xenobiotics. Frontiers Biosc. 2, d427-d437.
  • 12. Awasthi, S., Singhal, S.S., Srivastava, S.K., Zimniak, P., Bajpai, K.K., Saxena, M., Sharma, R., Ziller, S.A., 3rd, Frenkel, E.P, Singh, S.V., He, N.G. & Awasthi, Y.C. (1994) Adenosine triphosphate-dependent transport of doxorubicin, daunomycin, and vinblastine in human tissues by a mechanism distinct from the P-glycoprotein. J. Clin. Invest. 93, 958-965.
  • 13. Awasthi, S., Singhal, S.S., Srivastava, S.K., Torman, R.T., Zimniak, P., Bandorowicz- Pikula, J., Singh, S.V., Piper, J.T., Awasthi, Y.C. & Pikula, S. (1998) ATP-Dependent human erythrocyte glutathione-conjugate transporter. I. Purification, photoaffinity labeling, and kinetic characteristics of ATPase activity. Biochemistry 37, 5231-5238.
  • 14. Awasthi, S., Singhal, S.S., Pikula, S., Piper, J.T., Srivastava, S.K., Torman, R.T., Bandorowicz-Pikula, J., Lin, J.T., Singh, S.V., Zimniak, P. & Awasthi, Y.C. (1998) ATP-Dependent human erythrocyte glutathione-conjugate transporter. II. Functional reconstitution of transport activity. Biochemistry 37, 5239-5248.
  • 15. Awasthi, S., Singhal, S.S., Pandya, U., Gopal, S., Zimniak, P., Singh, S.V. & Awasthi, Y.C. (1999) ATP-Dependent colchicine transport by human erythrocyte glutathione conjugate transporter. Toxicol. Appl. Pharmacol. 155, 215-226.
  • 16. Awasthi, Y.C., Singhal, S.S., Zimniak, P., Piper, J.T., Pikula, S., Bandorowicz-Pikula, J., Lin, J.T., Srivastava, S.K., Singh, S.V. & Awasthi, S. (2000) Glutathione-linked pathways in drug resistance: Characterization and functional reconstitution of human erythrocyte glutathione-conjugate transporter. Clin. Chem. Enzym. Commun. 8, 431-448.
  • 17. Board, P.G. (1981) Transport of glutathione S-conjugate from human erythrocytes. FEBS Lett. 124, 163-165.
  • 18. Awasthi, Y.C., Misra, G., Rasasin, D.K. & Srivastava, S.K. (1983) Detoxification of xenobiotics by glutathione S-transferases in erythrocytes: The transport of the conjugate of glutathione and 1-chloro-2,4-dinitrobenzene. Brit. J. Hematol. 55, 419-425.
  • 19. Kondo, T., Murao, M. & Taniguchi, N. (1982) Glutathione S-conjugate transport using inside-out vesicles from human erythrocytes. Eur. J. Biochem. 125, 551-554.
  • 20. LaBelle, E.F., Singh, S.V., Srivastava, S.K. & Awasthi, Y.C. (1986) Dinitrophenyl glutathione efflux from human erythrocytes is primary active ATP-dependent transport. Biochem. J. 238, 443-449.
  • 21. Srivastava, S.K. & Beutler, E. (1969) The transport of oxidized glutathione from human erythrocytes. J. Biol. Chem. 244, 9-16.
  • 22. Awasthi, S., Cheng, J., Singhal, S.S., Saini, M.K., Pandya, U., Pikula, S., Bandorowicz- Pikula, J., Singh, S.V., Zimniak, P. & Awasthi, Y.C. (2000) Novel function of RLIP76: ATP-dependent transport of glutathione conjugates and doxorubicin. Biochemistry 39, 9327-9334.
  • 23. Prchal, J., Srivastava, S.K. & Beutler, E. (1975) Active transport of GSSG from reconstituted erythrocyte ghosts. Blood 46, 111-117.
  • 24. Kondo, T., Dale, G.L. & Beutler, E. (1981) Studies on glutathione transport utilizing inside-out vesicles prepared from human erythrocytes. Biochim. Biophys. Acta 645, 132-136.
  • 25. Kondo, T., Dale, G.L. & Beutler, E. (1980) Glutathione transport by inside out vesicles. Proc. Natl. Acad. Sci. U.S.A. 77, 6359-6362.
  • 26. Awasthi, Y.C., Garg, H.S., Dao, D.D., Partridge, C.A. & Srivastava, S.K. (1981) Enzymatic conjugation of erythrocyte glutathione with 1-chloro-2,4-dinitrobenzene: The fate of glutathione conjugate in erythrocytes and the effect of glutathione depletion on hemoglobin. Blood 58, 733-738.
  • 27. LaBelle, E.F., Singh, S.V., Srivastava, S.K. & Awasthi, Y.C. (1986) Evidence for different transport systems for oxidized glutathione and S-dinitrophenyl glutathione in human erythrocytes. Biochem. Biophys. Res. Commun. 139, 538-544.
  • 28. LaBelle, E.F., Singh, S.V., Ahmad, H., Wronski, L., Srivastava, S.K. & Awasthi, Y.C. (1988) A novel dinitrophenyl glutathione- stimulated ATPase is present in human erythrocyte membranes. FEBS Lett. 228, 53-56.
  • 29. Kumari, K., Ansari, N.H., Saxena, S., Awasthi, Y.C. & Srivastava, S.K. (1993) Low and high Km forms of dinitrophenyl glutathione-stimulated ATPase in bovine lens. Exp. Eye Res. 57, 243-247.
  • 30. Akerboom, T.P., Bartosz, G. & Sies, H. (1992) Low- and high-Km transport of dinitrophenyl glutathione in inside out vesicles from human erythrocytes. Biochim. Biophys. Acta 1103, 115-119.
  • 31. Bartosz, G., Sies, H. & Akerboom, T.P. (1993) Organic anions exhibit distinct inhibition patterns on the low-Km and high-Km transport of S-(2,4-dinitrophenyl)glutathione through the human erythrocyte membrane. Biochem. J. 292, 171-174.
  • 32. Pulaski, L. & Bartosz, G. (1995) Effect of inhibitors of transport of dinitrophenyl S-glutathione in human erythrocytes. Biochem. Mol. Biol. Int. 36, 935-942.
  • 33. Eckert, K.-G. & Eyer, P. (1986) Formation and transport of xenobiotic glutathione S-conjugates in red cells. Biochem. Pharmacol. 35, 325-329.
  • 34. Singhal, S.S., Sharma, R., Gupta, S., Ahmad, H., Zimniak, P., Radominska, A., Lester, R. & Awasthi, Y.C. (1991) The anionic conjugates of bilirubin and bile acids stimulate ATP hydrolysis by S-(dinitrophenyl)glutathione ATPase of human erythrocyte. FEBS Lett. 281, 255- 257.
  • 35. Kondo, T., Miyamoto, K., Gasa, S., Taniguchi, N. & Kawakami, Y. (1989) Purification and characterization of glutathione disulfide-stimulated Mg2+-ATPase from human erythrocytes. Biochem. Biophys. Res. Commun. 162, 1-8.
  • 36. Sharma, R., Gupta, S., Singh, S.V., Medh, R.D., Ahmad, H., LaBelle, E.F. & Awasthi, Y.C. (1990) Purification and characterization of dinitrophenylglutathione ATPase of human erythrocytes and its expression in other tissues. Biochem. Biophys. Res. Commun. 171, 155-161.
  • 37. Ishikawa, T. (1992) The ATP-dependent glutathione S-conjugate export pump. Trends Biochem. Sci. 17, 463-468.
  • 38. Saxena, M., Singhal, S.S., Awasthi, S., Singh, S.V., LaBelle, E.F., Zimniak, P. & Awasthi, Y.C. (1992) Dinitrophenyl S-glutathione ATPase purified from human muscle catalyzes ATP hydrolysis in the presence of leukotrienes. Arch. Biochem. Biophys. 298, 231- 237.
  • 39. Khanna, P., Kumari, K., Ansari, N.H. & Srivastava, S.K. (1994) ATP-dependent transport of glutathione-N-ethylmaleimide conjugate across erythrocyte membrane. Biochem. Med. Metab. Biol. 53, 105-114.
  • 40. Saxena, M. & Henderson, G.B. (1997) Multiple routes and regulation by tyrosine phosphorylation characterize the ATP-dependent transport of 2,4-dinitrophenyl S-glutathione in inside-out vesicles from human erythrocytes. Arch. Biochem. Biophys. 338, 173-182.
  • 41. Kondo, T., Kawakami, Y., Taniguchi, N. & Beutler, E. (1987) Glutathione disulfide-stimulated Mg2+-ATPase of human erythrocyte membranes. Proc. Natl. Acad. Sci. U.S.A. 84, 7373-7377.
  • 42. Awasthi, Y.C., Singhal, S.S., Gupta, S., Ahmad, H., Zimniak, P., Radominska, A., Lester, R. & Sharma, R. (1991) Purification and characterization of an ATPase from human liver which catalyzes ATP hydrolysis in the presence of the conjugates of bilirubin bile acids and glutathione. Biochem. Biophys. Res. Commun. 175, 1090-1096.
  • 43. Awasthi, Y.C., Saxena, M., Sharma, R., Singhal, S.S. & Ahmad, H. (1992) Role of glutathione S-transferase and dinitrophenyl S-glutathione ATPase (DNP-SG ATPase) in the protection of membranes from xenobiotics and oxidative stress. Int. J. Toxicol. Occup. Environ. Health 1, 77-85.
  • 44. Zimniak, P., Ziller, S.A., 3rd, Panfil, I., Radominska, A., Wolters, H., Kuipers, F., Sharma, R., Saxena, M., Moslen, M.T., Vore, M., Vonk, R., Awasthi, Y.C. & Lester, R. (1992) Identification of an anion-transport ATPase that catalyzes ATP hydrolysis in canalicular plasma membranes from normal rats and rats with conjugated hyperbilirubinemia (GY mutant) Arch. Biochem. Biophys. 292, 534-538.
  • 45. Pikula, S., Hayden, J.B., Awasthi, S., Awasthi, Y.C. & Zimniak, P. (1994) Organic anion- transporting ATPase of rat liver. I. Purification, photoaffinity labeling and regulation by phosphorylation. J. Biol. Chem. 269, 27566-27573.
  • 46. Pikula, S., Hayden, J.B., Awasthi, S., Awasthi, Y.C. & Zimniak, P. (1994) Organic anion-transporting ATPase of rat liver. II. Functional reconstitution of active transport and regulation by phosphorylation. J. Biol. Chem. 269, 27574-27579.
  • 47. Endicott, J.A. & Ling, V. (1989) The biochemistry of P-glycoprotein-mediated multidrug resistance. Annu. Rev. Biochem. 58, 137-171.
  • 48. Gottesman, M.M. & Pastan, I. (1993) Biochemistry of multidrug resistance mediated by the multidrug transporter. Annu. Rev. Biochem. 62, 385-427.
  • 49. Cole, S.P., Bhardwaj, G., Gerlach, J.H., Mackie, J.E., Grant, C.E., Almquist, K.C., Stewart, A.J., Kurz, E.U., Duncan, A.M. & Deeley, R.G. (1992) Overexpression of a transporter gene in a multidrug-resistant human lung cancer cell line. Science 258, 1650-1654.
  • 50. Lautier, D., Canitrot, Y., Deeley, R.G. & Cole, S.P. (1996) Multidrug resistance mediated by the multidrug resistance protein (MRP) gene. Biochem. Pharmacol. 52, 967-977.
  • 51. Johnstone, R.W., Ruefli, A.A. & Smyth, M.J. (2000) Multiple physiological functions for multidrug transporter P-glycoprotein? Trends Biochem. Sci. 25, 1-6.
  • 52. Saxena, M., Sharma, R., Singhal, S.S., Ahamad, H. & Awasthi, Y.C. (1991) The effect of doxorubicin on the transport of glutathione conjugates from human erythrocytes. Biochem. Arch. 7, 285-292.
  • 53. Winter, G.C., DeLuca, D.C. & Szumilo, H. (1994) 2,4-Dinitrophenol and carbonylcyanide p-trifluoromethoxyphenylhydrazone activate the glutathione S-conjugate transport ATPase of human erythrocyte membranes. Arch. Biochem. Biophys. 314, 17-22.
  • 54. DeLuca, D.C., Hinds, T. & Winter, C.G. (1997) Carbonyl cyanide phenylhydrazones as probes of the activator site of the human erythrocyte glutathione adduct transport ATPase. Arch. Biochem. Biophys. 342, 182-186.
  • 55. Jullien-Flores, V., Dorseuil, O., Romero, F., Letourneur, F., Saragosti, S., Berger, R., Tavitian, A., Gacon, G. & Camonis, J.H. (1995) Bridging Ral GTPase to Rho pathways. RLIP76, a Ral effector with CDC42/Rac GTPase-activating protein activity. J. Biol. Chem. 270, 22473-22477.
  • 56. Kondo, T., Yoshida, K., Urata, Y., Goto, S., Gasa, S. & Taniguchi, N. (1993) γ-Glutamylcysteine synthetase and active transport of glutathione S-conjugate are responsive to heat shock in K562 erythroid cells. J. Biol. Chem. 268, 20366-20372.
  • 57. Cantor, S.B., Urano, T. & Feig, L.A. (1995) Identification and characterization of Ral-binding protein 1, a potential downstream target of Ral GTPases. Mol. Cell. Biol. 15, 4578-4584.
  • 58. Park, S.H. & Weinberg, R.A. (1995) A putative effector of Ral has homology to Rho/Rac GTPase activating proteins. Oncogene 11, 2349-2355.
  • 59. Bauer, B., Mirey, G., Vetter, I.R., Garcia- Ranea, J.A., Valencia, A., Wittinghofer, A., Camonis, J.H. & Cool, R.H. (1999) Effector recognition by the small GTP-binding proteins Ras and Ral. J. Biol. Chem. 274, 17763- 17770.
  • 60. Feig, L.A., Urano, T. & Cantor, S. (1996) Evidence for a Ras/Ral signaling cascade. Trends Biochem. Sci. 21, 438-441.
  • 61. Chardin, P. (1988) The ras superfamily proteins. Biochimie 70, 865-868.
  • 62. Nakashima, S., Morinaka, K., Koyama, S., Ikeda, M., Kishida, M., Okawa, K., Iwamatsu, A., Kishida, S. & Kikuchi, A. (1999) Small G protein Ral and its downstream molecules regulate endocytosis of EGF and insulin receptors. EMBO J. 18, 3629-3642.
  • 63. Quaroni, A. & Paul, E.C. (1999) Cytocentrin is a Ral-binding protein involved in the assembly and function of the mitotic apparatus. J. Cell Sci. 112, 707-718.
  • 64. Pulaski, L., Jedlitschky, G., Leier, I., Buchholz, U. & Keppler, D. (1996) Identification of the multidrug-resistance protein (MRP) as the glutathione-S-conjugate export pump of erythrocytes. Eur. J. Biochem. 241, 644-648.
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